In French Patent Applications FR 8,301,223 (2,540,122) and FR 8,411,795 (2,568,254) have been described chemical compounds consisting of an oligonucleotide or an oligodeoxynucleotide comprising a concatentation of natural or modified nucleotides, that is to say beta-nucleotides, onto which is attached by a covalent bond at least one intercalating group, which possess the property of selectively blocking the expression of a gene and which, because of this, are particularly useful in therapy as antiviral, antibiotic, antiparasitic or antitumor substances.
In International Application PCT WO 83/01451, has been described a method for blocking the translation of messenger RNA (mRNA) into protein by hybridization of the mRNA with an oligonucleotide having the sequence complementary to the mRNA, the oligonucleotide being stabilized in phosphotriester form.
In International Application WO 88/04301 have been described oligonucleotides of alpha anomeric configuration having parallel pairings with complementary sequences.
Chemotherapy with antisense oligonucleotides relates to RNA or DNA targets of all living organisms (cells, bacteria, parasites, viruses or oncogenes).
The use of synthetic antisense oligonucleotides having the same structure as the natural nucleic acids is faced, mainly in biological medium, with problems of sensitivity to nucleases and cell penetration.
To overcome these limitations, oligonucleotide analogs capable of being more resistant to nucleases and of penetrating better into the cells across the cyto-plasmic membrane have been synthesized.
There has indeed been described in the prior art derivatives of oligonucleotide compounds resisting enzymatic degradations better, whose phosphate part was modified into thiophosphate or methyl phosphonate especially. However, these derivatives exhibit a chirality at the level of the phosphate capable of generating insoluble diastereoisomers.